advanced or metastatic solid tumors with homozygous deletion of MTAP 2-(4-amino-5H-pyrrolo-(3,2-d)pyrimidin-7-yl)-5-methylsulfanylmethylpyrrolidin-3,4-diol [Supplementary Concept]
Conditions
Interventions
S095035 (an oral methionine adenosyltransferase 2A [MAT2A] inhibitor) administered orally (PO) once daily (QD).
The trial will begin with a dose escalation starting at 50 mg. The DLT evaluation period
Administration, Oral
Sponsors
SADOU-DUBOURGNOUX Amel
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Males aged 18 years or older, or non-pregnant and non-lactating females. ECOG PS: 0-1. Patients with histologically confirmed advanced/metastatic solid tumors who have shown progression after prior treatment regimens and are considered unsuitable for standard therapies. Participants with pre-existing documented MTAP homozygous deletion in their tumor tissue Patients able to provide newly obtained tumor biopsy samples before Cycle1Day1 and during treatment. Patients with adequate hematologic, renal, and hepatic function based on assessments within 7 days prior to the first dose of the investigational drug.
Exclusion criteria
Exclusion criteria: Patients unable to take oral medication or with medical conditions or surgical history that may affect drug absorption. Patients participating in another interventional study or within less than 5 half-lives of another investigational drug. (Participation in non-interventional registries or epidemiological studies is allowed.) Patients with active secondary cancer (except for specific non-invasive cancers). Patients who have undergone major surgery within 4 weeks prior to the first dose of the investigational drug or have not recovered from the side effects of surgery. Patients with severe or uncontrolled active acute or chronic infections. Patients with active brain metastases (symptomatic brain metastases or leptomeningeal disease). Participants who have received systemic anticancer treatment or radiotherapy less than 2 weeks before the first dose of S095035. Patients with medical conditions that exacerbate clinically significant photosensitivity (e.g., solar urticaria, lupus erythematosus).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-limiting toxicities(DLTs) associated with S095035 administration during the first cycle of treatment Adverse events(AEs) and serious adverse events, changes in safety laboratory results, changes in the physical examination, vital signs, electrocardiogram(ECG), and Eastern Cooperative Oncology Group(ECOG) performance status(PS) | — |
Secondary
| Measure | Time frame |
|---|---|
| The following plasma PK parameters (but not limited to): Area under the concentration-time curve from time zero to the last measurable concentration (AUC0-t), AUC from time zero to infinity, AUC over one dosing interval at steady state (AUCtau,ss), time to reach maximum concentration (Tmax), maximum concentration (Cmax), trough concentration (Ctrough), half-life (t half), apparent volume of distribution (Vd/F), and apparent clearance (CL/F) (if data is available). Changes from baseline in plasma concentrations of S-adenosylmethionine (SAM) and other PD biomarker candidates during treatment. New guidelines for evaluating the therapeutic effect of solid tumors (RECIST version 1.1) and investigator assessment: Objective response rate (ORR) Clinical benefit rate (CBR) (CBR = Complete Response [CR] + Partial Response [PR] + Stable Disease [SD] for 6 months or more) Duration of response (DoR) Time to response (TTR) | — |
Countries
Australia, Japan, US
Contacts
Public Contactclinical operation department International center for therapeutic research
Nihon Servier Company Limited
Outcome results
None listed